Project Summary: In the United States, the American Cancer Society estimates that, in 2015, there will be 45,780 new cases of oral cavity and pharyngeal cancer. Despite new and improved treatments (surgery, radiation, and chemotherapy), the overall 5-year survival rate for oral cavity and pharyngeal cancer in the United States is only 63%. Over 8,650 children and adults still die every year of oral cancers, and many survivors experience treatment-related side effects for many years after diagnosis. Currently, the operating surgeon relies on experience and preoperative imaging to mentally piece together where best to cut. This can lead to inconsistent narrow tumor margins or result in excessive tissue resection in order to clear surgical margins. The long-term goal of this research is to reduce cancer recurrence while minimizing end-organ damage by robotically performing tumor resection with precise and consistent tumor margins. The following specific aims will enable the development of this technology and demonstrate feasibility: Aim 1: Develop and evaluate a precise tumor marking method to guide tumor resection with intra- operative surgical imaging. Aim 2: Compare supervised autonomous tumor resection surgery to current manual and robotic techniques. This research has the potential to significantly improve outcome of tumor surgery independent of operating surgeon. Starting with oral squamous cell carcinoma (SCC), this approach of tumor marking and supervised autonomous tumor resection could be beneficial in all tumor surgery.